Hypoxanthine Phosphoribosyl Transferase 1 Is Upregulated, Predicts Clinical Outcome and Controls Gene Expression in Breast Cancer

Abstract

Hypoxanthine phosphoribosyl transferase 1 (<i>HPRT1</i>) is traditionally believed to be a housekeeping gene; however, recent reports suggest that it is upregulated in several cancers and is associated with clinical outcomes. <i>HPRT1</i> is located on chromosome X and encodes the HPRT enzyme, which functions in recycling nucleotides to supply for DNA and RNA synthesis in actively dividing cells. Here, we used transcriptomic analyses to interrogate its expression across all known cancer types and elucidated its role in regulating gene expression in breast cancer. We observed elevated <i>HPRT1</i> RNA levels in malignant tissues when compared to normal controls, indicating its potential as a diagnostic and prognostic marker. Further, in breast cancer, the subtype-specific analysis showed that its expression was highest in basal and triple-negative breast cancer, and <i>HPRT1</i> knockdown in breast cancer cells suggested that <i>HPRT1</i> positively regulates genes related to cancer pathways. Collectively, our results essentially highlight the importance of and change the way in which <i>HPRT1</i>'s function is studied in biology, warranting careful examination of its role in cancer.